Incidence rates of invasive lobular breast carcinomas (ILBC) have increased steadily in the United States since 1977, whereas the trend of increasing incidence of ductal breast cancer has plateaued since 1987. This rise in lobular tumors has occurred specifically among women over age 50. The use of combined estrogen-progestin hormone replacement therapy (CHRT) has also risen steadily over this time period, and recent analyses from two case-control investigations suggest that postmenopausal women who use CHRT may have an increased risk of ILBC, whereas there is no relationship of CHRT to ductal cancer. Few epidemiologic studies have assessed how known or suspected risk factors for breast cancer differ across different histologic types, but such investigations are important because there are likely to be multiple pathways leading to the development and progression of breast cancer of different histologic types. The primary objectives of this proposed study are to confirm recent preliminary findings that CHRT is associated with lobular breast cancer in a large population-based study, to assess this relationship in greater detail, and to explore mechanisms for this association. We propose to conduct a case-control study of 900 women aged 55-79 who have been diagnosed with breast cancer (450 lobular, 450 ductal) and 450 population-based controls who reside in the three county Seattle-Puget Sound metropolitan area of western Washington. The specific questions to be addressed are: (1) Is the use of CHRT associated with an increase in the incidence of invasive lobular breast cancer in women aged 55-79. (2) Is the use of CHRT associated with an increase in the incidence of invasive ductal breast cancer in women aged 55-79? (3) Do the duration, patterns and/or recency of CHRT use influence he size of the association? (4) Is the use of CHRT associated with alteration in the histologic characteristics, tumor cell proliferation, or expression of steroid hormone receptors, oncogenes, and cell cycle and cell death regulator proteins of lobular and ductal breast cancers?